{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:48:21Z","timestamp":1782755301237,"version":"3.54.5"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Tokyo University of Science Grant for President\u00e2\u20ac\u2122s Research Promotion"},{"DOI":"10.13039\/501100020963","name":"Moonshot Research and Development Program","doi-asserted-by":"publisher","award":["JPMJMS2022-21"],"award-info":[{"award-number":["JPMJMS2022-21"]}],"id":[{"id":"10.13039\/501100020963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08936"],"award-info":[{"award-number":["20K08936"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K12517"],"award-info":[{"award-number":["24K12517"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant-in-Aid for Early-Career Scientists","award":["23K14352"],"award-info":[{"award-number":["23K14352"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a grant from the Institute for Environmental & Gender-Specific Medicine"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Cell\u2013cell junctions (CCJs) are essential for maintaining epithelial integrity, and adhesion-related molecules have long been implicated in breast cancer progression. However, the subtype-specific prognostic significance of CCJ-related gene expression patterns within individual intrinsic breast cancer subtypes has not been systematically characterized. We analyzed 179 genes annotated to the Gene Ontology term \u201ccell\u2013cell junction organization\u201d (GO:0045216) across intrinsic breast cancer subtypes using the METABRIC and The Cancer Genome Atlas (TCGA) datasets. Subtype-specific prognostic CCJ genes were identified using multivariate Cox proportional hazards models for disease-specific survival and integrated into CCJ gene expression signatures. The prognostic performance was validated in an independent cohort (SCAN-B). Elevated CCJ signature scores were associated with poorer survival across subtypes, with particularly strong effects in Luminal B (LumB) and Basal-like (Basal) tumors. Person-year analyses indicated that high CCJ scores predicted an increased incidence of early recurrence (0\u20135 years) in these aggressive subtypes. Pathway enrichment analyses revealed that high-score tumors exhibited upregulation of extracellular matrix organization and matrisome-related pathways. Single-cell RNA sequencing further demonstrated that LumB CCJ genes (e.g.,\n                    <jats:italic>PARD6B<\/jats:italic>\n                    ,\n                    <jats:italic>CDH3<\/jats:italic>\n                    ) were predominantly expressed in tumor epithelial cells, whereas the Basal CCJ signature reflected contributions from epithelial (e.g.,\n                    <jats:italic>MARVELD2<\/jats:italic>\n                    ) and endothelial (e.g.,\n                    <jats:italic>RAMP2<\/jats:italic>\n                    ) cells. Collectively, CCJ signatures stratify prognosis and capture subtype-specific cellular and microenvironmental features in breast cancer.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352254","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:33:18Z","timestamp":1782754398000},"page":"e0352254","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell\u2013cell junction gene signatures as subtype-specific prognostic biomarkers in breast 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